Synthesis of malhamensilipin A exploiting iterative epoxidation/chlorination: experimental and computational analysis of epoxide-derived chloronium ions

We report a 12-step catalytic enantioselective formal synthesis of malhamensilipin A (3) and diastereoisomeric analogues from (E)-2-undecenal. The convergent synthesis relied upon iterative epoxidation and phosphorus(V)-mediated deoxydichlorination reactions as well a titanium-mediated epoxide-openi...

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Main Authors: Saska, J., Lewis, W., Paton, R.S., Denton, R.M.
Format: Article
Published: Royal Society of Chemistry 2016
Online Access:https://eprints.nottingham.ac.uk/35946/
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author Saska, J.
Lewis, W.
Paton, R.S.
Denton, R.M.
author_facet Saska, J.
Lewis, W.
Paton, R.S.
Denton, R.M.
author_sort Saska, J.
building Nottingham Research Data Repository
collection Online Access
description We report a 12-step catalytic enantioselective formal synthesis of malhamensilipin A (3) and diastereoisomeric analogues from (E)-2-undecenal. The convergent synthesis relied upon iterative epoxidation and phosphorus(V)-mediated deoxydichlorination reactions as well a titanium-mediated epoxide-opening to construct the C11-C16 stereohexad. The latter transformation occurred with very high levels of stereoretention regardless of the C13 configuration of the parent epoxide, implicating anchimeric assistance of either the γ- or δ-chlorine atoms, and the formation of chloretanium or chlorolanium ions, respectively. A computational analysis of the chloronium ion intermediates provided support for the involvement of chlorolanium ions, whereas the potential chloretanium ions were found to be less likely intermediates on the basis of their greater carbocationic character
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institution University of Nottingham Malaysia Campus
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spelling nottingham-359462020-05-04T18:08:02Z https://eprints.nottingham.ac.uk/35946/ Synthesis of malhamensilipin A exploiting iterative epoxidation/chlorination: experimental and computational analysis of epoxide-derived chloronium ions Saska, J. Lewis, W. Paton, R.S. Denton, R.M. We report a 12-step catalytic enantioselective formal synthesis of malhamensilipin A (3) and diastereoisomeric analogues from (E)-2-undecenal. The convergent synthesis relied upon iterative epoxidation and phosphorus(V)-mediated deoxydichlorination reactions as well a titanium-mediated epoxide-opening to construct the C11-C16 stereohexad. The latter transformation occurred with very high levels of stereoretention regardless of the C13 configuration of the parent epoxide, implicating anchimeric assistance of either the γ- or δ-chlorine atoms, and the formation of chloretanium or chlorolanium ions, respectively. A computational analysis of the chloronium ion intermediates provided support for the involvement of chlorolanium ions, whereas the potential chloretanium ions were found to be less likely intermediates on the basis of their greater carbocationic character Royal Society of Chemistry 2016-08-02 Article PeerReviewed Saska, J., Lewis, W., Paton, R.S. and Denton, R.M. (2016) Synthesis of malhamensilipin A exploiting iterative epoxidation/chlorination: experimental and computational analysis of epoxide-derived chloronium ions. Chemical Science . ISSN 2041-6539 http://pubs.rsc.org/en/content/articlelanding/2016/sc/c6sc03012b#!divAbstract doi:10.1039/C6SC03012B doi:10.1039/C6SC03012B
spellingShingle Saska, J.
Lewis, W.
Paton, R.S.
Denton, R.M.
Synthesis of malhamensilipin A exploiting iterative epoxidation/chlorination: experimental and computational analysis of epoxide-derived chloronium ions
title Synthesis of malhamensilipin A exploiting iterative epoxidation/chlorination: experimental and computational analysis of epoxide-derived chloronium ions
title_full Synthesis of malhamensilipin A exploiting iterative epoxidation/chlorination: experimental and computational analysis of epoxide-derived chloronium ions
title_fullStr Synthesis of malhamensilipin A exploiting iterative epoxidation/chlorination: experimental and computational analysis of epoxide-derived chloronium ions
title_full_unstemmed Synthesis of malhamensilipin A exploiting iterative epoxidation/chlorination: experimental and computational analysis of epoxide-derived chloronium ions
title_short Synthesis of malhamensilipin A exploiting iterative epoxidation/chlorination: experimental and computational analysis of epoxide-derived chloronium ions
title_sort synthesis of malhamensilipin a exploiting iterative epoxidation/chlorination: experimental and computational analysis of epoxide-derived chloronium ions
url https://eprints.nottingham.ac.uk/35946/
https://eprints.nottingham.ac.uk/35946/
https://eprints.nottingham.ac.uk/35946/